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Reduced insulin signaling maintains electrical transmission in a neural circuit in aging flies

Partridge, L; Augustin, H; Adcott, J; Kerr, F; Vincent, A; Boucrot, E; (2017) Reduced insulin signaling maintains electrical transmission in a neural circuit in aging flies. PLOS 10.1371/journal.pbio.2001655. Gold open access

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Abstract

Lowered insulin/insulin-like growth factor (IGF) signaling (IIS) can extend healthy lifespan in worms, flies, and mice, but it can also have adverse effects (the “insulin paradox”). Chronic, moderately lowered IIS rescues age-related decline in neurotransmission through the Drosophila giant fiber system (GFS), a simple escape response neuronal circuit, by increasing targeting of the gap junctional protein innexin shaking-B to gap junctions (GJs). Endosomal recycling of GJs was also stimulated in cultured human cells when IIS was reduced. Furthermore, increasing the activity of the recycling small guanosine triphosphatases (GTPases) Rab4 or Rab11 was sufficient to maintain GJs upon elevated IIS in cultured human cells and in flies, and to rescue age-related loss of GJs and of GFS function. Lowered IIS thus elevates endosomal recycling of GJs in neurons and other cell types, pointing to a cellular mechanism for therapeutic intervention into aging-related neuronal disorders.

Type: Article
Title: Reduced insulin signaling maintains electrical transmission in a neural circuit in aging flies
Open access status: An open access publication
DOI: 10.1371/journal.pbio.2001655
Publisher version: http://dx.doi.org//doi.org/10.1371/journal.pbio.20...
Language: English
Additional information: Copyright: © 2017 Augustin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, (https://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1569417
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